RESUMO
OBJECTIVE: To investigate the clinical role of hypermethylation of suppressor of cytokine signaling (SOCS) on typical myeloproliferative disease (MPD) patients and its mechanism. METHODS: Methylation specific PCR was used to detect SOCS1, 2, 3 methylation, direct DNA sequencing was performed to detect JAK2V617F mutation, real-time fluorescence quantitative PCR were applied to evaluate transcriptional activity of SOCS1, 2, 3. RESULTS: Among 100 MPD patients, hypermethylation of SOCS1 was detected in 27 (27%), hypermethylation of SOCS2 in 9 (9%), hypermethylation of SOCS3 in 34 (34%); JAK2V617F mutation in 64 (64%). Hypermethylation of SOCS1, 3 greatly inhibited gene expression compared with unmethylated ones (P < 0.05). Presence of JAK2V617F mutation markedly down-regulated SOCS1, 3 gene mRNA expression compared with wild JAK2V617F (P < 0.05). CONCLUSION: Hypermethylation of SOCS1, 3 and JAK2V617F mutation exist in MPD, which inhibited SOCS1, 3 gene expression. SOCS hypermethylation and JAK2V617F mutation can activate JAK-STAT signaling pathways, these observations may provide a potential therapeutic direction.
Assuntos
Metilação de DNA , Transtornos Mieloproliferativos/metabolismo , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Janus Quinase 2/genética , Masculino , Pessoa de Meia-Idade , Mutação , Transtornos Mieloproliferativos/genética , RNA Mensageiro/genética , Transdução de Sinais , Proteínas Supressoras da Sinalização de Citocina/genética , Adulto JovemRESUMO
BACKGROUND & OBJECTIVE: There is no standard salvage regimen for patients with recurrent and refractory non-Hodgkin's lymphoma (NHL) so far. This study was to investigate the efficacy of DICE (dexamethasone, isofosfamide, cisplatin, and etoposide) regimen on recurrent and refractory NHL, and observe the adverse events. METHODS: Clinical records of 80 patients with recurrent and refractory NHL, who failed to get remission from CHOP regimen (cyclophosfamide, vincristine, and donaurubicin) and accepted DICE as a salvage regimen for 6 cycles, were reviewed. Of the 80 patients, 25 were T-cell original, and the other 55 were B-cell original. The efficacy of DICE regimen and adverse events were evaluated. RESULTS: The total response rate (RR) of these 80 patients was 56.3%. The complete remission (CR) rate was 27.5%.The total response rate was 48.0% for T-cell NHL and 60.0% for B-cell NHL. The CR rate was 16.0% for T-cell NHL and 32.7% for B-cell NHL. Myelosuppression, nausea, vomit, alopecia, and electrolytes disorder were major adverse events, and could be cured after treatment. No chemotherapy-related death occurred. CONCLUSION: DICE regimen is effective in treating recurrent and refractory NHL.
